Tyrosinase-related protein 2-derived peptide–Human leukocyte antigen complex (TRP-2 peptide–HLA complex)

Tyrosinase-related protein 2 (TRP-2), also known as dopachrome tautomerase (DCT), is an enzyme essential for melanin biosynthesis in melanocytes (UniProt: P40126). Peptides derived from the intracellular processing of TRP-2 are loaded onto Human Leukocyte Antigen (HLA) molecules and presented on the cell surface. In the context of malignancy, particularly melanoma, these TRP-2 peptide–HLA complexes function as tumor-associated antigens (TAAs) that can be recognized by cytotoxic T lymphocytes (CTLs) (PMID: 10426997). Because TRP-2 is highly expressed in melanoma cells and relatively restricted to melanocytes, it is a prominent target for immunotherapy. Current therapeutic approaches include cancer vaccines designed to expand TRP-2-specific T-cells and adoptive cell therapies using T-cells engineered with TCRs specific to the TRP-2 peptide–HLA complex (PMID: 21602448). However, targeting this complex carries risks of off-tumor toxicity, such as vitiligo or ocular inflammation, due to the presence of TRP-2 in normal pigmented tissues.

Other names

Dopachrome tautomerase-derived peptide–HLA complexDCT peptide–HLA complexTRP2-MHC complexTRP-2 antigenL-dopachrome Delta-isomerase-derived peptide–HLA complex

The complex acts as a ligand for specific T-cell receptors (TCRs). Therapeutic agents either provide the peptide to stimulate endogenous T-cells (vaccines) or use engineered TCRs to recognize the complex, leading to the directed lysis of cells expressing the antigen (PMID: 8552639).